Nuclear alkylation of anilins

ABSTRACT

The present invention provides a process for the production of phenylamines alkylated in the ortho and/or para positions by alkyl groups of 1 to 4 carbon atoms and unsubstituted on the amino group, which comprises reacting a phenylamine having an ortho and/or para position available for alkylation with an alkanol of 1 to 4 carbon atoms in the vapour phase and with heating to a temperature of from 350* to 450*C, using a catalyst selected from aluminium oxide and aluminium oxide/molybdenum oxide mixed catalyst in which the amount of molybdenum oxide is approximately from 0.01 to 20 percent by weight, which catalyst has a minimum surface area 50 m2/g.

United States Patent [191 Evans et al.

m1" 3,868,420 [451 Feb, 25, 1975 NUCLEAR ALKYLATION OF ANILINS [73]Assignee: Sandoz Ltd., Basel, Switzerland [22] Filed: Aug. 14, 1972 I[211 App]. No.: 280,353

[30] Foreign Application Priority Data Aug. 20, 1971 Switzerland12299/71 Oct. 14, 1971 Switzerland....; l51l9/7l [52] US. Cl. 260/578,260/671 C, 252/466 R [51] Int. Cl. C07c 39/06 [58] Field of Search260/578 [56] References Cited UNITED STATES PATENTS 3,201,486 8/1965Bielawski et al 260/578 3,365,347 l/l968 Lund et al. 260/578 3,733,3655/1973 Yeakey et al.' 260/578 OTHER PUBLICATIONS Morrison and Boyd.,Organic Chemistry, pp. 160, 161.

Industrial and Engineering Chemistry, Vol. 3, No. 7 pg. 1579-1584.

Primary Examiner-Donald G. Daus Assistant Examiner-D. Wheeler Attorney,Agent, or FirmGerald D. Sharkin; Richard E. Vila; Joseph J. Borovian 571ABSTRACT The present invention provides a process for the production ofphenylamines alkylated in the ortho and/or para positions by valkylgroups of l to 4 carbon atoms and unsubstituted on the amino group,which comprises reacting a phenylamine having an ortho and/or paraposition available for alkylation with an alkanol of I to 4 carbon atomsin the vapour phase and with heating to a temperature of from 350 to450C, using a catalyst selected from aluminium oxide and alumin-.

ium oxide/molybdenum oxide mixed catalyst in which the amount ofmolybdenum oxide is approximately from0.0l to 20 percent by weight,which catalyst has a minimumsurface area 50 m /g.

8 Claims, 2 Drawing Figures PATENTEDFEBZS ms sum 1 hr 2 l l lPAIENIEBraazsms I 3,868,420 sum 2 j 2 FIGURE 2 NUCLEAR ALKYLATION OFANILINS IMPROVEMENTS IN OR RELATING TO ORGANIC COMPOUNDS This inventionrelates to a process for the production of phenylamines alkylated in theortho andl/or para positions.

The present invention provides a process for the production ofphenylamines alkylated in the ortho and/or para positions by alkylgroups of 1 to 4 carbon atoms and unsubstituted on the amino group,which comprises reacting a phenylamine having an ortho and/or paraposition available for alkylation with an alkanol of 1 to 4 carbon atomsin the vapour phase and with heating to a temperature of from 350 to 450C, using a catalyst selected from aluminium oxide and aluminiumoxide/molybdenum oxide mixed catalyst in which the amount of molybdenumoxide is approximately from 0.01 to 20 percent by weight, which catalysthas a minimum surface area of 50 m /g.

It has been found especially advantageous to use a catalyst with asurface area of from 150 to 300m /g. The aluminium oxide catalysts canbe produced by known methods. The aluminum oxide/molybdenum oxidecatalysts, which are especially preferred, can also be produced inaccordance with known methods, e.g., by impregnation of Al O with anammonium molyb date solution, drying and if necessary calcination (cf.,for example, Journal of Catalysis 1969), page 202, column 1 which givesrise to an Al o catalyst containing M The preferred amount of molybdenumoxide is from 1 to 2.5 percent by weight.

For'the process of this invention, aniline itself or an anilinesubstituted by alkyl of 1 to 4 carbon atoms on the amino group or on thenucleus which is present in the vapour phase at the reaction temperatureis suitable. For instance, phenylamines optionally substituted by one ortwo alkyl radicals can be employed, which may be primary, secondary ortertiary phenylamines. The alkyl radicals of major interest are thosewith l or 2 carbon atoms. The following aromatic amines may be named asexamples: aniline, toluidines (preferably oor p-toluidine),xylidines(preferably 2,4- or 2,6-xylidine), ethyl anilines (e.g. oor p-ethylaniline), ethyl methyl aniline, N-ethyl aniline, N-methyl aniline andN,N- dimethyl aniline. For example in the formation ofmesidine, aniline,toluidine, xylidine or their mixtures are preferably used. It is to beunderstood that when a N- substituted compound is used as startingmaterial the alkanol to be used should correspond to the N-alkylsubstituent. The alkanol is employed to best effect in at least thestoichiometric amount, but preferably in amounts not greater than in a:1 molar ratio. For example, for the production mesidine from aniline,preferably 4 to 7 mols of methanol are used, while when starting fromtoluidine preferably 3 to 6 mols of methanol are employed.

The catalyst, which of course must be present in the solid state at thereaction temperature, is used effectively in the form of globules, solidor hollow cylinders, pellets, or in some other form suitable for fillingreactor vessels. The reaction vessel, which is generally a column ortube, is packed with the catalyst so that the vaporised reactants comeinto immediate contact with the largest possible surface area ofcatalyst.

The reaction can be conducted isothermally or adiabatically or withpartial removal of heat. The pressure is of secondary importance for theprogress of the reaction; practical considerations make it convenient towork at atmospheric pressure, but the use of higher pressures ispracticable. It is of special advantage to carry out the disclosedprocess continuously.

- The process of this invention enables phenylamines alkylated in thenucleus to be produced in high yield in relatively short times comparedwith the known processes. For example, the optium yield of mesidine maybe, e.g., 75 to 80 percent of theory; if the N-methylated by-productsare recycled in a continuous operating system an increase in the yieldto approximately 80 to 85 percent of theory is realizable.

The by-products which may be formed in the reaction of this inventioninclude hexamethyl benzene, which may be present in amounts to 7percent, isoduridine, and decomposition products, notably gases such asCO CO, CH.,, and hydrogen. Minor amounts of readily volatile amines alsomay be formed in the course of the reaction. The volatile by-productscan be easily removed, or destroyed by combustion. The formation ofby-products depends largely on the activity of the catalyst and inparticular on the time-span of its use, further factors are thequantitative relation of the reactants and the reaction temperature.

If the process of this invention is operated continuously, it isadvisable to regenerate the catalyst from time to time. An effectiveregeneration treatment is to direct air'heated to 350 to 450C over thecatalyst to burn the organic substances it has absorbed. As the heat ofcombustion in the reaction .is often very high, the temperature of thecatalyst has to be closely con trolled, and it may be found necessary todilute the air further with an inert gas, for example nitrogen.

An installation for the continuous operation of the disclosed process isshown in diagrammatic form in FIG. 1. of the accompanying drawings. Itcomprises a storage tankv l for the aromatic amine and a second storagetank 2 for the alcohol (alkylating agent), an evaporator 3 and a furtherevaporator 4, both for the phenylamine, and an evaporator 5, furtherevaporator 6 and superheater 7 for the alcohol. The amine is conductedfrom 1 through 3 and 4 and the alcohol from 2 through 5, 6 and 7. Thealcohol and the amine then pass on for mixing and the mixture isconveyed, with or without the introduction of circulating gas (14),through the preheater 8 to a series of reactors 9 filled with catalyst.(In the diagram there are four of these: 9a, 9b, 9c and 9d, but thenumber may be smaller or greater than this, e.g. one, two, up to 10,depending on their size, the nature of the starting products, the typeof catalyst, the temperature, and the rate of circulation of the gas).The reactors may be connected to each other through'intermediate coolers10 to enable the temperature of the circulating reactants and thereaction products to be reduced at need. The reactors may be heated todifferent temperatures, in which case the scale of temperature is chosento suit the reactants and the catalyst, the first reactor or reactorsbeing set at a lower temperature, e.g. 250350C, while at least one ofthe following reactors is maintained at a temperature from 350 to 450C.For the production of mesidine a suitable temperature setting is:reactor 9a 250-360C,

reactor 9b 320400C, reactor 9c 340420C, reactor A cooler (condenser) 11is provided for the mixture of reaction products and a gas/liquidseparator 12 for separation of the cooled gaseous by-products. Theliquid reaction products are conducted to 17, while the gaseousby-produc'ts are led to the gas washer 13 where, for example, ammonia iswashed out. The gases can be removed through the collecting tube 15 to16 5 ture from reactor 9c 440C, entry temperature into reand ifnecessary burned; gas for recycling can be reactor 9d 405C, exittemperature from reactor 9d turned by the pump 14. In 17, which is aseparator for 435C). The reaction gases from reactor 9d are con- C uamine and r, the Crude amine is separated densed in the condenser cooler11 and the condensate from the water of reaction and any waterofdecomposiooled t 60C, The uneondensed gases are separated tionpresent, and conducted into the storage tank 18. i th /li id Separator12, urified f any The nucleo-alkylated amine is freed from unreacted t ied lid or liquid in the gas washer l3 and reamine and by-products in therectifier A t y g turned, with circulating gas, to the reaction cycle.The device especially suitable for the rectification of mesigas id th hth Separating vessel 15 to be Chile is shown in 2 0f the accompanyingdrawingsburned (16). From the gas/liquid separator 12 the col- From 18crude final product is led into the first rectrfyrl5 l d li id fl i th vl 17, wh r th r d ihg column, in which unalkylated or P f i y alkylatedresidue is separated from the water of reaction. The amine is obtainedas p fraction i f and crude mesidine is then conveyed into the storagetank cycled-t0 The fraction containing the nucleo- 18 (62 parts byweight per hour). It is rectified in the alkylated amine and the lessvolatile by-products is led tifi 19 (FIG 2) into the Second ratifyingcolumn, Where the nucieo- 20 After the aforedescribed continuous processhas alkylated amine is obtained as top fraction (a), while been iOperation f about 10 to 20 d r n ti the less volatile byproducts areseparated as the bottom 7 'of the catalyst is necessary to maintain itsactivity at the (sump) fraction (b). The rectifying device shown indesired level. For the regeneration treatment, the reac- FIG. 2 has twocolumns, but a single column which is tor is first cooled with nitrogengas, thereby bringing capable of separating several fractions can beused, or the temperature of the catalyst to about 350C. The rearectifier with more than two columns, as for example actor gas is thencirculated, the optimum amount being when unalkylated or partiallyalkylated products have about 200 litres per hour and kilogram ofcatalyst. Subto be fractionated. sequently air is added to thecirculating gas in an opti- The following Examples illustrate theprocess of this mum amount of about litres per hour and kilograminvention in a continuous operating system, using an 30 of catalyst. Theratio of air to circulating gas is limited installation corresponding tothat described above. by the maximum permissible catalyst temperature,which should not exceed 450C. After about 24 hours, EXAMPLE 1regeneration is complete. The amount of circulated gas can then becarefully diminished and the supply finally From the storage tank 1 51parts by weight of pturned off. During this phase too the catalysttemperatoluidine per hour are conducted into the thin-film ture shouldnot increase to above 450C. Afterwards, evaporator 3, and from thestorage tank 2 49 parts by air is directed through the catalyst at therate of 30 to weight of methanol per hour into the thin-filmevaporalitres per hour and kilogram of catalyst until the CO tor 5. Inthe further evaporators 4 and 6 respectively, content of the spent airfalls to less than 2 percent. Reany drops falling down the previousevaporators are va- 40 generation is then complete and the productionplant porized. The methanol vapour is superheated further in can be setfor further operation as described above. 7. The two gas currents arethen united and conducted, In Table 1 below further examples of theproduction with the circulating gas, into the preheater 8, where theprocess are detailed. F 2 .fie W.-. Table l Exple Catalyst (220 mlg)Temperature Rate of Yield of Composition of crude mesidine No. TypeParts by in "C feed in crude mesidine Pre- Mesidine Hexalsoweight kg/hin kg/h fraction methyl duridine benzene l A1 0, 175 260-440 5,1Paratolu- 6,2 7 77 9 6 idine 4,9 Methanol 2 A1203 120 265-430 5,0Paratolu- 6,3 19 5 +l% M00, idine 5,0 Methanol 3 A1 0 250-440 4,1Aniline 5,2 33 59 6 +l% M003 7,0 Methanol 4 A1203 120 250-435 5,0Paratolu- 6,5 20 77 3 +2% M003 i he 4,5 Methanol 5 M10 120 250-425 4.5Aniline 5,8 21 70 7 +l% M00 6.5 Methanol 6 Al 0" I20 250-430 0.5 2.6Xyli- 6. 27 (v5 )4- (1 71' 4,0 Aniline 6,4 Methanol gas mixture isheated up to 260C for entry into the first reactor 9a. On leaving thisreactor the temperature of entry temperature into reactor 9c 390C, exittempera- MPP 7 If a mixture of 194 parts of methanol, 163 parts ofptoluidine and 45 parts of a top fraction from distillation is employedunder the same reaction conditions as in Example 1, 259 parts of crudemesidine are obtained. Distillation of the crude mesidine gives threefractions, namely a top fraction of 45 parts, 163 parts of pure mesidineand Si parts of residue. As the amount of distillate used in thereaction is the same as that obtained at the end of the process, theyield of mesidine from ptoluidine is 80 percent of theory.

Further examples of phenylamines alkylated in the nucleus which can beproduced in accordance with this invention re. i snin. th 9!. Qwin .Ia!1i What is claimed is:

1. A process for the production of phenylamine alkyl- TABLE II Startingproducts Maximum Yield in Example Mol temperature percent number AlcoholAmine ratio Catalyst in 0. Final product of theory 8 CHSOH 1TH: 511A1203 445 I\1IH2 3O C2H5 Ha C- CgHs CH 9 omen 1 1m '431 A1 0; 430 1 11i?HaC- -CH I 02H: 2H;

10 CzHsOII NH2 3:1 A1203 380 NIB 1) l plus 2.5% M00: H3O- 1h0- (lgll5 LC- II: (1:

| CH 11 CHsOH 1,2:1 A1 0; 445

a I 20 0 Ha HaC- CI-I3 N Hg 12 OHEOH 2:1 M20;

u": IlaC- ll:i

The A1 0 catalyst containing 1 percent M00 is produced as follows: partsby weight of A1 0 catalyst in the form of round tablets are thoroughlymixed with ated in the ortho and/or para positions by alkyl groups of 1to 4 carbon atoms and unsubstituted on the amino group, which comprisesthe step of reacting a phenylamine having an ortho and/or para positionavailable for alkylation with an alkanol of l to 4 carbon atoms in thevapour p as and wi e in .@aiqmw turs 318A29i 7 mm; s

of from 350 to 450C, in the presence of aluminum oxavailable orthoand/or para position with methanol in ide/molybdenum oxide mixedcatalyst in which the the vapor phase and with heating to a temperatureof amount of molybdenum oxide is approximately from from 350 to 450C. inthe presence of an aluminum 0.01 to 20 percent by weight, which catalysthas a minioxide/molybdenum oxide mixed catalyst which the mum surfacearea Of SQm /g. amount of molybdenum oxide is approximately from 2. Aprocess according to claim 1, in which the cam- 0.01 to percent byweight, which catalyst has a minilyst has a surface area of from lSQ toQQQ rn /g mum surface area of 50m /g.

6. A process according to claim 5, in which a phenylis used containingfrom I to percent by weight of amine selected from anllme, toluidmes,xyhdmes and molybdenum oxide. l0 mixtures of any two or more thereof isreacted with methanol to produce mesidine.

. A process according to clalml wherein the al- 7. A process accordingto claim 6, in which pkanol.phenylamme mol ratio is at leaststolchiometnc toluidine is reacted w1th methanol to produce .mesibut notgreat er than 10.1. I dine 5. A process according to claim 1 for theproduction 15 A process according to Claim 7, in which the of Phenylammemethylated the olitho andlor'p'fua lecular ratio of methanol top-toluidine is in the range positions and unsubstituted on the ammogroup, which from 2:1 to 10m comprisesthe step of reacting a phenylaminehaving an A fig 3. A process according to claim 2, in which a catalyst

1. A PROCESS FOR THE PRODUCTION OF PHENYLAMINE ALKYLATED IN THE ORTHOAND/OR PARA POSITIONS BY ALKYL GROUPS OF 1 TO 4 CARBON ATOMS ANDUNSUBSTITUTED ON THE AMINO GROUP, WHICH COMPRISES THE STEP OF REACTING APHENYLAMINE HAVING AN ORTHO AND/OR PARA POSITION AVAILABLE FORALKYLATION WITH AN ALKANOL OF 1 TO 4 CARBON ATOMS IN THE VAPOR PHASE ANDWITH HEATING TO A TEMPERATURE OF FROM 350* TO 450*C, IN THE PRESENCE OFALUMINUM OXIDE/MOLYBDENUM OXIDE MIXED CATALYST IN WHICH THE AMOUNT OFMOLYBDENUM OXIDE IS APPROXIMATELY FROM 0.01 TO 20 PERCENT BY WEIGT,WHICH CATALYST HAS A MINIMUM SURFACE AREA OF 50M2/G.
 2. A processaccording to claim 1, in which the catalyst has a surface area of from150 to 300 m2/g.
 3. A process according to claim 2, in which a catalystis used containing from 1 to 2.5 percent by weight of molybdenum oxide.4. A process according to claim 1 wherein the alkanol: phenylamine molratio is at least stoichiometric but not greater than 10:1.
 5. A processaccording to claim 1 for the production of phenylamine methylated in theortho and/or para positions and unsubstituted on the amino group, whichcomprises the step of reacting a phenylamine having an available orthoand/or para position with methanol in the vapor phase and with heatingto a temperature of from 350* to 450*C. in the presence of an aluminumoxide/molybdenum oxide mixed catalyst which the amount of molybdenumoxide is approximately from 0.01 to 20 percent by weight, which catalysthas a minimum surface area of 50m2/g.
 6. A process according to claim 5,in which a phenylamine selected from aniline, toluidines, xylidines andmixtures of any two or more thereof is reacted with methanol to producemesidine.
 7. A process according to claim 6, in which p-toluidine isreacted with methanol to produce mesidine.
 8. A process according toclaim 7, in which the molecular ratio of methanol to p-toluidine is inthe range from 2:1 to 10:1.